High prevalence of Plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern Malawi

Abstract

BackgroundIn endemic areas, many people experience asymptomatic Plasmodium infections, particularly older children and adults, but their transmission contribution is unknown. Though not the exclusive determinant of infectiousness, transmission from humans to mosquitoes requires blood meals containing gametocytes. Gametocytes often occur at submicroscopic densities, challenging measurement in human populations. More sensitive molecular techniques allow better characterization of gametocyte epidemiologic patterns.MethodsApproximately 30 households were selected from each of eight sites in southern Malawi during two cross-sectional surveys. Blood was sampled from 623 people during the dry season and 896 the following rainy season. Among people PCR-positive for Plasmodium falciparum, mature gametocytes were detected by qRT-PCR. Regression models evaluated predictors of gametocyte carriage and density in the total population and among those with PCR-positive infections.ResultsThe prevalence of gametocyte carriage by molecular testing was 3.5% during the dry season and 8.6% during the rainy season, and by microscopy 0.8 and 3.3%, respectively. Nearly half of PCR-positive infections carried gametocytes, regardless of recent symptom status. Among P. falciparum-infected people, only living in unfinished houses and age were significantly associated with gametocyte presence. Infected people in unfinished houses had higher odds of carrying gametocytes (OR 2.24, 95% CI 1.16–4.31), and 31% (95% CI 3–65%) higher gametocyte density than those in finished houses. School-age children (5–15 years), had higher odds than adults (≥16 years) of having gametocytes when infected (OR 2.77, 95% CI 1.47–5.19), but 31% (95% CI 11–47%) lower gametocyte density. Children <5 years did not have significantly higher odds of gametocyte carriage or density when infected than adults.ConclusionsSchool-age children frequently carry gametocytes in communities of southern Malawi and represent an under-recognized reservoir of infection. Malaria elimination strategies should address these frequently asymptomatic reservoirs, especially in highly endemic areas. Improved household construction may also reduce the infectious reservoir.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1587-9) contains supplementary material, which is available to authorized users.

Molecular detection and quantification of Plasmodium falciparum gametocytes carriage in used RDTs in malaria elimination settings in northern Senegal

“…This study revealed that P. falciparum mature gametocytes can also be sourced from used RDTs. In addition to quantifying the number of DNA amplification cycles, SYBR Green makes it possible to estimate the number of gametocyte copies [9,19,20]. The number of copies would have allowed providing more precision on the estimation of the gametocyte density in this study [20].…”

“…The presence of mature gametocytes (stage V) in the human peripheral blood is the determining factor in the maintenance and increase of malaria transmission [1]. In Senegal, progress in the fight against malaria led the program to become part of the regional elimination of malaria by introducing primaquine in the management of the disease in the north of the country in order to reduce malaria gametocyte carriage in the population and block the transmission of the disease [2,3].…”

“…Gametocytes are sexual forms of the parasite that are transmitted from the human host to mosquito vectors and thus perpetuate the transmission of malaria [4,5,6]. The passage of gametocytes to vectors is possible even in sub-microscopic low-density situations in human blood (<4 gametocytes / μl) [1,4,7]. The detection and quantification of specific gametocytes from modern molecular techniques such as the quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) have shown a high frequency of sub-microscopic densities [1,7].…”

“…The passage of gametocytes to vectors is possible even in sub-microscopic low-density situations in human blood (<4 gametocytes / μl) [1,4,7]. The detection and quantification of specific gametocytes from modern molecular techniques such as the quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) have shown a high frequency of sub-microscopic densities [1,7]. Even after treatment with antimalarials, the gametocytes persist for several weeks after the clearance of asexual parasite forms with longevity depending on the nature and dose of the treatment administered as well as the immune response of the host [6].…”

“…Since mosquito infection requires the presence of gametocytes in humans, knowledge of the epidemiology of gametocyte carriage is an essential parameter for assessing malaria transmission and predicting infectiousness in vectors [1,7,8]. Some molecular techniques are used today for the detection and quantification of gametocytes [9,10]. The complexity and cost of these tests limits their use in resource areas.…”